Investigation of a role for ghrelin signaling in binge-like feeding in mice under limited access to high-fat diet

King, Samantha J.; Rodrigues, Trevor; Watts, A.; Murray, E. Selkirk; Wilson, A.; Abizaid, Alfonso

doi:10.1016/j.neuroscience.2016.01.004

Cited by 29 publications

(29 citation statements)

References 73 publications

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“…At this early stage, 2‐hour HF intake increases across the binge‐like eating events and then stabilises . The current observations, together with previous results showing that GHSR‐deficient mice do not increase 2‐hour HF intake in the same binge‐like eating protocol, indicate that GHSR activity affects HF intake escalation. Intake escalation is a complex behaviour observed in the early stages of binge eating models, as well as in rodents successively exposed to drugs of abuse.…”

Section: Discussionsupporting

confidence: 77%

“…By contrast to WT mice, GHSR‐deficient mice do not display conditioned place preference for HF diet upon caloric restriction or chronic stress, whereas mice with expression of GHSR selectively in catecholaminergic cells, including the dopamine VTA neurones, show a conditioned place preference for HF diet after chronic stress similar to that seen in WT mice . Previous studies showing that GHSR‐deficient mice exhibit a smaller binge‐like HF intake also reported that these mice display a concomitant reduced activation of the mesolimbic pathway . Thus, it appears reasonable to hypothesise that centrally‐injected GHSR inverse agonists reduce binge‐like HF intake as a result of its action on the mesolimbic pathway.…”

Section: Discussionmentioning

confidence: 94%

“…Studies in rodents provided additional evidence linking GHSR activity and binge eating . In particular, satiated GHSR‐deficient mice daily and time‐limited exposed to high‐fat (HF) diet display an attenuated binge‐like HF intake compared to WT mice . Interestingly, the lack of GHSR reduces binge‐like intake over the initial accesses to palatable food, when daily HF intake gradually escalates and is recognised as the transition period from a controlled to an uncontrolled behaviour .…”

Section: Introductionmentioning

confidence: 99%

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Growth hormone secretagogue receptor signalling affects high‐fat intake independently of plasma levels of ghrelin andLEAP2, in a 4‐day binge eating model

Cornejo

Castrogiovanni

Schiöth

et al. 2019

J Neuroendocrinology

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The growth hormone secretagogue receptor (GHSR) is a G protein‐coupled receptor that is highly expressed in the central nervous system. GHSR acts as a receptor for ghrelin and for liver‐expressed antimicrobial peptide 2 (LEAP2), which blocks ghrelin‐evoked activity. GHSR also displays ligand‐independent activity, including a high constitutive activity that signals in the absence of ghrelin and is reduced by LEAP2. GHSR activity modulates a variety of food intake‐related behaviours, including binge eating. Previously, we reported that GHSR‐deficient mice daily and time‐limited exposed to a high‐fat (HF) diet display an attenuated binge‐like HF intake compared to wild‐type mice. In the present study, we aimed to determine whether ligand‐independent GHSR activity affects binge‐like HF intake in a 4‐day binge‐like eating protocol. We found that plasma levels of ghrelin and LEAP2 were not modified in mice exposed to this binge‐like eating protocol. Moreover, systemic administration of ghrelin or LEAP2 did not alter HF intake in our experimental conditions. Interestingly, we found that central administration of LEAP2 or K‐(D‐1‐Nal)‐FwLL‐NH2, which are both blockers of constitutive GHSR activity, reduced binge‐like HF intake, whereas central administration of ghrelin or the ghrelin‐evoked GHSR activity blockers [D‐Lys3]‐GHRP‐6 and JMV2959 did not modify binge‐like HF intake. Taken together, current data indicate that GHSR activity in the brain affects binge‐like HF intake in mice independently of plasma levels of ghrelin and LEAP2.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Growth hormone secretagogue receptor signalling affects high‐fat intake independently of plasma levels of ghrelin andLEAP2, in a 4‐day binge eating model

Cornejo

Castrogiovanni

Schiöth

et al. 2019

J Neuroendocrinology

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show abstract

“…Accordingly, administration of ghrelin increases while disruption of the ghrelin system using antagonists or GHSR knockout (KO) animals decreases the consumption of palatable foods [36,101,102,103,104,105,106]. Furthermore, ghrelin injections facilitate the development of conditioned place preferences (CPP) and enhance bar press break points for rewarding foods [37,107].…”

Section: Introductionmentioning

confidence: 99%

Clarifying the Ghrelin System’s Ability to Regulate Feeding Behaviours Despite Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand

Edwards

Abizaid

2017

IJMS

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Ghrelin is a hormone predominantly produced in and secreted from the stomach. Ghrelin is involved in many physiological processes including feeding, the stress response, and in modulating learning, memory and motivational processes. Ghrelin does this by binding to its receptor, the growth hormone secretagogue receptor (GHSR), a receptor found in relatively high concentrations in hypothalamic and mesolimbic brain regions. While the feeding and metabolic effects of ghrelin can be explained by the effects of this hormone on regions of the brain that have a more permeable blood brain barrier (BBB), ghrelin produced within the periphery demonstrates a limited ability to reach extrahypothalamic regions where GHSRs are expressed. Therefore, one of the most pressing unanswered questions plaguing ghrelin research is how GHSRs, distributed in brain regions protected by the BBB, are activated despite ghrelin’s predominant peripheral production and poor ability to transverse the BBB. This manuscript will describe how peripheral ghrelin activates central GHSRs to encourage feeding, and how central ghrelin synthesis and ghrelin independent activation of GHSRs may also contribute to the modulation of feeding behaviours.

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“…Likewise, the impulsivity behaviour observed in eating disorders can be increased by ghrelin action within the VTA (Anderberg et al, ). Moreover, the study of a growth‐hormone secretagogue receptor KO mouse model under a limited access to HFD protocol, which emulates select components of binge eating in humans, confirms the role for ghrelin‐growth‐hormone secretagogue receptor signalling in driving HFD consumption and mediation of reward circuitries (King et al, ; Valdivia, Cornejo, Reynaldo, De Francesco, & Perello, ). Overall, GHSR KO mice consumed fewer calories from HFD and had reduced activation of the NAc shell, but not core (King et al, ).…”

Section: Eating Beyond Metabolic Needs: the Nonhomeostatic Role Of Pementioning

confidence: 61%

Unravelling the role and mechanism of adipokine and gastrointestinal signals in animal models in the nonhomeostatic control of energy homeostasis: Implications for binge eating disorder

Novelle

Diéguez

2018

Euro Eating Disorders Rev

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Central and peripheral signals regulating energy homeostasis interact tightly with neuronal pathways to modulate the hedonic component of food intake. Dysregulation of these interactions could explain the development of binge eating disorder (BED) and/or obesity and the increasing incidence of food addiction. In this review, we have highlighted the crucial role of peripheral hormones, such as leptin and ghrelin, among others, in these nonhomeostatic pathways. We have also emphasised the relevance of central cannabinoid pathway and lateral hypothalamus, with orexin and melanin‐concentrating hormone neurons, as the critical hub controlling motivation and reward. Throughout the manuscript, we have focused on mechanisms learned from animal models of BED/food addiction in order to understand how these peripheral signals can modulate the motivation to eat. Understanding these mechanisms could help us to develop new treatment options for BED and/or obesity.

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Investigation of a role for ghrelin signaling in binge-like feeding in mice under limited access to high-fat diet

Cited by 29 publications

References 73 publications

Growth hormone secretagogue receptor signalling affects high‐fat intake independently of plasma levels of ghrelin andLEAP2, in a 4‐day binge eating model

Growth hormone secretagogue receptor signalling affects high‐fat intake independently of plasma levels of ghrelin andLEAP2, in a 4‐day binge eating model

Clarifying the Ghrelin System’s Ability to Regulate Feeding Behaviours Despite Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand

Unravelling the role and mechanism of adipokine and gastrointestinal signals in animal models in the nonhomeostatic control of energy homeostasis: Implications for binge eating disorder

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